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conferenceseries
.com
Volume 9
Journal of Biotechnology & Biomaterials
ISSN: 2155-952X
JOINT EVENT
February 28-March 02, 2019 | Berlin, Germany
5
th
International Conference on
Enzymology and Protein Chemistry
&
22
nd
Global Congress on
Biotechnology
Biotechnology 2019
Enzymology 2019
February 28-March 02, 2019
&
Engineered Erwinase with possible fewer adverse effects for treatment of acute lymphoblastic
leukemia
Iris Munhoz Costa, Débora Custódio Moura, Adalberto Pessoa Jr.
and
Gisele Monteiro
University of Sao Paulo, Brazil
A
cute lymphoblastic leukemia (ALL) is the most frequent neoplasm in children and adolescents. Treatment of the disease
is performed with L-asparaginase (ASNase), an enzyme obtained from the bacteria Escherichia coli and Erwinia
chrysanthemi (Erwinase). ASNase hydrolyzes L-asparagine and prevents tumor cells from obtaining this amino acid from
the bloodstream for protein synthesis, leading to ALL cell death by apoptosis. However, both formulations are associated
with a high rate of adverse effects as the production of anti-asparaginase antibodies and hypersensitivity, which compromise
the efficacy of the treatment. The development of mutant proteoforms from commercially available bacterial enzymes may
contribute to the development of an enzyme with lower adverse effects. Therefore, we created a mutant library using the
ASNase of E. chrysanthemi by error prone PCR, and a double mutant proteoform (DM) presented higher specific activity for
L-asparagine and a 30% increase in the kcat in relation to the wild-type (WT) enzyme. In addition, DM enzyme showed less
recognition by anti-asparaginase antibodies and is able to kill the same amount of ALL cell line MOLT-4 than WT enzyme,
using a smaller amount of protein. The results indicated that the DM enzyme has cytotoxic potential and may have fewer
adverse effects.
Biography
Iris Munhoz Costa is a PhD student in the graduate program in Pharmaceutical Technology-Biochemistry in the School of Pharmaceutical Sciences at University of
São Paulo. She works with biopharmaceutical research for the treatment of acute lymphoblastic leukemia. She has obtained her Master’s degree in Pharmaceutical
Technology-Biochemistry at University of São Paulo in 2015; Graduation in Pharmacy and Biochemistry at Universidade Paulista in 2012. She was a student of
scientific initiation in the Department of Pharmaceutical Biochemical Technology in the Faculty of Pharmaceutical Sciences at the University of São Paulo in the
area of molecular biology and antioxidant response in 2011.
iris.munhoz@hotmail.comIris Munhoz Costa et al., J Biotechnol Biomater 2019, Volume 9
DOI: 10.4172/2155-952X-C2-116